Keywords
Endoscopic ultrasound - fine-needle aspiration cytology - gastric glomus tumor - immunohistochemistry
Introduction
Glomus tumor (GT) is a rare mesenchymal tumor arising from the neuroarterial structure
known as glomus body and commonly located in the extremities and soft tissue.[1] Gastric GT (GGT) is a subepithelial tumor first described by de Busscher et al. There rarity and overlapping of clinical and conventional radiological features
with the other more common submucosal gastric tumors result into difficult preoperative
accurate diagnosis. Endoscopic ultrasound-guided fine-needle aspiration cytology (EUS-FNAC)
emerged as one of the best modalities for preoperative diagnosis. However, in smaller
lesion, inadequacy of the material may limit to perform immunohistochemistry (IHC)
or cell block preparation and hurdle in confirmation of the diagnosis. Till date,
to the best of our knowledge, only seven cases were correctly diagnosed by EUS-FNAC,
possibly due to adequate material to perform IHC.[2] We describe a case of GGT in a 60-year-old female provisionally diagnosed on cytology
with confirmation on histology and IHC panel.
Case Report
A 60-year-old female referred to the outpatient department of our hospital with the
chief complaints of progressive dysphagia for both solid and liquid associated with
pain for the last 4 months. She observed partial relief from the symptoms on intake
of proton pump inhibitors. No history of any other associated symptoms such as vomiting,
regurgitation, gastrointestinal (GI) bleed, malena, or jaundice was present. However,
significant weight loss of about 5 kg was noted during the period of illness. Her
hemogram and liver and kidney function tests were within normal limits. The upper
GI endoscopy revealed extensive ulcerations in mid and lower third of the esophagus
with a small hiatus hernia at the lower esophageal sphincter. The stomach showed a
large submucosal mass lesion in the anterior wall of the body region. D1 and D2 mucosa
appeared normal. Contrast-enhanced computed tomography showed a well-defined, rounded
endoexophytic lesion with heterogeneously moderate enhancement measuring 26 mm × 25
mm and peripheral calcifications in the anterior wall of stomach [Figure 1a]. An EUS was also done along with FNAC, which showed a large predominantly hypoechoic
lesion arising from the second layer of stomach measuring 2.6 cm × 2.2 cm [Figure 1b] and [c]. No penetration into the deeper layer was noted. The FNAC was reported as benign
lesion suggestive of GT. A wide local excision of the lesion was planned. Intraoperatively,
a 2 cm × 2 cm mass was seen in the body of the stomach which was excised with 1 cm
margin [Figure 2]. A frozen section confirmation of the margin was done which was reported negative
for malignancy. No lymph nodes were seen. Postoperative course was uneventful, and
the patient was discharged after 5 days. Currently, at 1-year follow-up, the patient
is fine and symptom-free.
Figure 1: (a) Contrast-enhanced computed tomography scan showing a well-defined rounded
endoexophytic lesion with heterogeneously moderate enhancement and peripheral calcifications
in the anterior wall of stomach, (b and c) endoscopic ultrasound showing a large predominantly
hypoechoic lesion arising from the second layer of the stomach. No penetration into
the deeper layer was noted
Figure 2: Intraoperative image showing a circumscribed globular mass in the body of
the stomach
Pathological features
FNAC smears revealed a moderately cellular aspirate with few caught up smooth muscle
fibers [Figure 3a] in the background. The tumor was comprised of monomorphic round-to-oval cells arranged
in tiny clusters. The cells were displaying hyperchromatic to vesicular chromatin
with occasional prominent nucleoli [Figure 3b], arrow] and moderate amount of eosinophilic cytoplasm [Figure 3c]. No significant pleomorphism, spindling, epithelioid appearance, salt and pepper
chromatin, mitosis, or necrosis was seen. However, due to limitations of aspirate,
further IHC evaluation or cell block making was not feasible. Considering the clinical,
radiological, and cytological features together, a provisional diagnosis of GT was
made and a histological correlation was advised.
Figure 3: Fine-needle aspiration cytology smears displaying (a) a moderately cellular
aspirate with few caught up smooth muscle fibers (arrow) in the background (Giemsa,
×200), (b) tumor comprises monomorphic round-to-oval cells showing hyperchromatic
to vesicular nuclei with occasional prominent nucleoli (arrow) and moderate amount
of eosinophilic cytoplasm (Geimsa, ×400) and (c) (H and E, ×400)
On gross examination, tumor appeared as circumscribed globular mass measuring 25 mm
× 20 mm. On microscopy, hematoxylin and eosin-stained sections showed a cellular tumor
located in the muscularis propria of the body of the stomach [Figure 4a]. The cells were round-to-oval with vesicular chromatin, prominent nucleoli [Figure 4b], and moderate amount of eosinophilic cytoplasm. No mitosis or necrosis was seen.
An IHC panel was applied to differentiate GT from GI stromal tumor and carcinoid.
The cells revealed diffuse positivity for smooth muscle actin, HHF-35, caldesmon,
and synaptophysin (weak positive). However, CD117, CD34, chromogranin-A, desmin, and
S-100 were negative [Figure 4c], [d], [e], [f]. The MIB-1 labeling index was approximately 1%–2%. Based on morphology and IHC,
final diagnosis of benign GT was offered.
Figure 4: Photomicrographs showing (a) a cellular tumor located in the muscularis
propria of the body of the stomach (H and E, ×40), (b) cells appear round-to-oval
with vesicular chromatin, prominent nucleoli, and moderate amount of eosinophilic
cytoplasm (H and E, ×400), and immunopositivity for (c) HHF-35, (d) smooth muscle
actin, (e) caldesmon, and (f) synaptophysin (IHC, ×400)
Discussion
GGTs are very rare which account for 1% of mesenchymal tumors of the GI tract.[3] GGT usually occurs in the fifth to sixth decade of life and shows a female preponderance.
They may be detected incidentally or presents with nonspecific symptoms such as upper
abdominal pain, vomiting, or upper GI bleeding. These are mostly solitary, circumscribed,
arise from the submucosa or muscularis propria and show a predilection for antrum.
On computed tomography, they show a strong enhancement in the arterial phase which
persists in the portal venous and delayed phases, thus reflecting their hypervascular
nature.[4] However, this radiological feature is not typical of GT and shared by more common
carcinoid as well as GI stromal tumors. Similarly, on EUS imaging, they appear as
hypoechoic well-defined mass which is common to other mesenchymal tumor. Therefore,
imaging modalities are not very useful for certain diagnosis of these lesions. However,
incorporation of FNAC in EUS mostly achieved a preoperative diagnosis and overcame
the limitations of imaging which is necessary for the optimal surgical interventions.
On cytology smear, GGT appears as sheets of round-to-oval monomorphic cells with hyperchromatic
nuclei, inconspicuous nucleoli, and moderate amount of cytoplasm. Few naked nuclei
may also be seen. However, salt and pepper chromatin typical characteristic of neuroendocrine
tumors is absent which is an important clue to differentiate the two most logical
and common differentials. In our case, based on cytological features, we made a provisional
diagnosis of GT, due to inadequacy of material to perform immunocytochemistry or cell
block preparation. The diagnosis was later confirmed on histological examination and
IHC of the resected specimen. GGT shows immunopositivity for vimentin, smooth muscle
actin, HHF-35, and caldesmon. Sometimes, a weak nonspecific positivity for synaptophysin
may be noted which was also seen in the present case.[5] However, other neuroendocrine markers such as chromogranin-A, CD56, or PGP9.5 do
not reveal positivity.
GGTs are mostly benign neoplasms classified into three types based on different components
as solid GT, glomangioma, and glomangiomyoma.[6] Folpe et al.[7] proposed the criteria for malignant GT which includes deep location, size ≥2 cm,
moderate-to-high nuclear grade, atypical mitotic figures, and mitotic figures ≥5/50
high-power fields. GGTs have a different clinical course in comparison to peripherally
located soft-tissue GTs. Thambi et al.[8] suggested that size >5 cm is more important than cellular atypia and mitotic activity
in GGTs. A wide local resection, mostly laparoscopic with negative margins, is the
treatment of choice. However, large tumor size or features suggesting a malignant
potential may lead to a subtotal gastrectomy.
To conclude, GGT is usually a benign mesenchymal tumor which can be correctly diagnosed
by EUS-FNAC, provided adequacy of the aspirate in addition to localizing the layer
of its origin. Correct preoperative diagnosis is required to perform an optimum conservative
wide local excision and avoid any major surgical intervention.
